scholarly journals Hyaluronic Acid–Decorated Liposomes as Innovative Targeted Delivery System for Lung Fibrotic Cells

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3291 ◽  
Author(s):  
Laura Pandolfi ◽  
Vanessa Frangipane ◽  
Claudia Bocca ◽  
Alessandro Marengo ◽  
Erika Tarro Genta ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Targeted Delivery ◽  
Immune Modulation ◽  
Bronchiolitis Obliterans Syndrome ◽  
Molecular Weights ◽  
Matrix Deposition ◽  
Targeting Efficiency ◽  
Healthy Donors ◽  
Extracellular Matrix Deposition ◽  
Collagen Tissue

Collagen Tissue Disease–associated Interstitial Lung Fibrosis (CTD-ILDs) and Bronchiolitis Obliterans Syndrome (BOS) represent severe lung fibrogenic disorders, characterized by fibro-proliferation with uncontrolled extracellular matrix deposition. Hyaluronic acid (HA) plays a key role in fibrosis with its specific receptor, CD44, overexpressed by CTD-ILD and BOS cells. The aim is to use HA-liposomes to develop an inhalatory treatment for these diseases. Liposomes with HA of two molecular weights were prepared and characterized. Targeting efficiency was assessed toward CTD-ILD and BOS cells by flow cytometry and confocal microscopy and immune modulation by RT-PCR and ELISA techniques. HA-liposomes were internalized by CTD-ILD and BOS cells expressing CD44, and this effect increased with higher HA MW. In THP-1 cells, HA-liposomes decreased pro-inflammatory cytokines IL-1β, IL-12, and anti-fibrotic VEGF transcripts but increased TGF-β mRNA. However, upon analyzing TGF-β release from healthy donors-derived monocytes, we found liposomes did not alter the release of active pro-fibrotic cytokine. All liposomes induced mild activation of neutrophils regardless of the presence of HA. HA liposomes could be also applied for lung fibrotic diseases, being endowed with low pro-inflammatory activity, and results confirmed that higher MW HA are associated to an increased targeting efficiency for CD44 expressing LFs-derived from BOS and CTD-ILD patients.

scholarly journals Hyaluronic Acid-Decorated Chitosan Nanoparticles for CD44-Targeted Delivery of Everolimus

2018 ◽  
Vol 19 (8) ◽  
pp. 2310 ◽  
Author(s):  
Enrica Chiesa ◽  
Rossella Dorati ◽  
Bice Conti ◽  
Tiziana Modena ◽  
Emanuela Cova ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Targeted Delivery ◽  
Chitosan Nanoparticles ◽  
Mesenchymal Cells ◽  
Bronchiolitis Obliterans Syndrome ◽  
Process Conditions ◽  
Uptake Mechanism ◽  
Organ Rejection ◽  
Matrix Deposition

Bronchiolitis obliterans syndrome (BOS), caused by lung allograft-derived mesenchymal cells’ abnormal proliferation and extracellular matrix deposition, is the main cause of lung allograft rejection. In this study, a mild one-step ionotropic gelation method was set up to nanoencapsulate the everolimus, a key molecule in allograft organ rejection prevention, into hyaluronic acid-decorated chitosan-based nanoparticles. Rationale was the selective delivery of everolimus into lung allograft-derived mesenchymal cells; these cells are characterized by the CD44-overexpressing feature, and hyaluronic acid has proven to be a natural selective CD44-targeting moiety. The optimal process conditions were established by a design of experiment approach (full factorial design) aiming at the control of the nanoparticle size (≤200 nm), minimizing the size polydispersity (PDI 0.171 ± 0.04), and at the negative ζ potential maximization (−30.9 mV). The everolimus was successfully loaded into hyaluronic acid-decorated chitosan-based nanoparticles (95.94 ± 13.68 μg/100 mg nanoparticles) and in vitro released in 24 h. The hyaluronic acid decoration on the nanoparticles provided targetability to CD44-overexpressing mesenchymal cells isolated from bronchoalveolar lavage of BOS-affected patients. The mesenchymal cells’ growth tests along with the nanoparticles uptake studies, at 37 °C and 4 °C, respectively, demonstrated a clear improvement of everolimus inhibitory activity when it is encapsulated in hyaluronic acid-decorated chitosan-based nanoparticles, ascribable to their active uptake mechanism.

scholarly journals The Effect of Hyaluronic Acid on MMP-9 Expression in Trabecular Meshwork Cell Culture of Patient with Primary Open Angle Glaucoma

2017 ◽  
Vol 3 (1) ◽  
pp. 38
Author(s):  
Cicih Komariah ◽  
Ma’sum Effendi ◽  
Hidayat Sujuti
Keyword(s):  
Cell Culture ◽  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Trabecular Meshwork ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Open Angle ◽  
Trabecular Meshwork Cell ◽  
Matrix Deposition ◽  
Extracellular Matrix Deposition

In primary open angle glaucoma, decrease of hyaluronic acid level is related to extracellular matrix deposition of trabecular meshwork. Extracellular matrix deposition will increase humor aqueous outflow resistance which in turn increase the intraocular pressure. MMP-9 as one of matrix metalloproteinase (MMP) family, has a high potency to degrade the extracellular matrix. The expression of MMP-9 can be activated by hyaluronic acid through its binding with CD44 as hyaluronic main receptor. The aim of this research is to determine the effect of hyaluronic acid on MMP-9 expression in trabecular meshwork cell culture of patient with primary open angle glaucoma by immunocytochemical method. Trabecular meshwork cell culture were exposed to hyaluronic acid at four different concentration (0mg/ml, 1 mg/mL, 3 mg/mL, 6 mg/mL). After 24 hours incubated, we find a significant difference of MMP-9 expression between control group and group with hyaluronic acid. There was significant correlation between hyaluronic acid and MMP-9 expression. Hyaluronic acid exposure will increase MMP-9 expression in trabecular meshwork cell culture. This finding suggest that hyaluronic acid can influence the resistance of humor aqueous outflow in trabecular meshwork by up-regulating MMP-9 expression, and therefore will increase extracellular matrix degradation.Key words : hyaluronic acid, primary open angle glaucoma, MMP-9

scholarly journals Effects of the Molecular Weight of Hyaluronic Acid in a Carbon Nanotube Drug Delivery Conjugate

2020 ◽  
Vol 8 ◽  
Author(s):  
Silvia Arpicco ◽  
Michał Bartkowski ◽  
Alessandro Barge ◽  
Daniele Zonari ◽  
Loredana Serpe ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Molecular Weight ◽  
Hyaluronic Acid ◽  
Anticancer Agents ◽  
Targeted Delivery ◽  
Molecular Weights ◽  
Good Biocompatibility ◽  
Highly Hydrophobic ◽  
Cluster Of Differentiation ◽  
Walled Carbon Nanotubes

Hyaluronic acid (HA) is a ubiquitous biopolymer involved in many pathophysiological roles. One HA receptor, the cluster of differentiation CD44 protein, is often overexpressed in tumor cells. As such, HA has attracted considerable interest in the development of drug delivery formulations, given its intrinsic targetability toward CD44 overexpressing cells. The present study is focused on examining the correlation of HA molecular weight with its targetability properties. A library of conjugates obtained by linking the amino group of the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) to the carboxylic residues of HA of different molecular weight (6.4, 17, 51, 200, and 1,500 kDa) were synthesized and fully characterized. The HA-DMPE conjugates were then used to non-covalently functionalize the highly hydrophobic single-walled carbon nanotubes (CNT), and further encapsulate the anticancer drug doxorubicin (DOX). Our results show that the complexes DOX/CNT/HA-DMPE maintain very good and stable dispersibility. Drug release studies indicated a pH-responsive release of the drug from the nanocarrier. Cell viability tests demonstrated that all HA modified CNTs have good biocompatibility, and specific targeting toward cells overexpressing the CD44 receptor. Among all the molecular weights tested, the 200 kDa HA showed the highest increase in cellular uptake and cytotoxic activity. All these promising attributes make CNT/HA200-DMPE a “smart” platform for tumor-targeted delivery of anticancer agents.

scholarly journals Hyaluronic Acid-Coated MTX-PEI Nanoparticles for Targeted Rheumatoid Arthritis Therapy

Crystals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 321
Author(s):  
Shenghui Zhong ◽  
Peng Liu ◽  
Jinsong Ding ◽  
Wenhu Zhou
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Targeted Delivery ◽  
High Dose ◽  
One Pot ◽  
Inflammatory Site ◽  
Pei Nanoparticles ◽  
Toxic Reactions

Methotrexate (MTX) is an anchor drug for the treatment of rheumatoid arthritis (RA); however, long-term and high-dose usage of MTX for patients can cause many side effects and toxic reactions. To address these difficulties, selectively delivering MTX to the inflammatory site of a joint is promising in the treatment of RA. In this study, we prepared MTX-PEI@HA nanoparticles (NPs), composed of hyaluronic acid (HA) as the hydrophilic negative electrical shell, and MTX-linked branched polyethyleneimine (MTX-PEI) NPs as the core. MTX-PEI@HA NPs were prepared in the water phase by a one-pot method. The polymeric NPs were selectively internalized via CD44 receptor-mediated endocytosis in the activated macrophages. In the in vivo mice mode study, treatment with MTX-PEI@HA NPs mitigated inflammatory arthritis with notable safety at a high dose of MTX. We highlight the distinct advantages of aqueous-synthesized NPs coated with HA for arthritis-selective targeted delivery, thus verifying MTX-PEI@HA NPs as a promising MTX-based nanoplatform for treatment of RA.

A multifunctional substance P-conjugated chitosan hydrochloride hydrogel accelerates full-thickness wound healing by enhancing synchronized vascularization, extracellular matrix deposition, and nerve regeneration

2021 ◽  
Author(s):  
Hao Li ◽  
Mengna Li ◽  
Pei Liu ◽  
Kai-Yang Wang ◽  
Haoyu Fang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Full Thickness ◽  
Matrix Deposition ◽  
Chitosan Hydrochloride ◽  
Reconstructive Microsurgery ◽  
Extracellular Matrix Deposition ◽  
Advanced Biomaterials ◽  
Native Skin ◽  
Full Thickness Wound

Due to the native skin limitations and the complexity of reconstructive microsurgery, advanced biomaterials are urgently required to promote wound healing for severe skin defects caused by accidents and disasters....

scholarly journals Well-defined single polymer nanoparticles for the antibody-targeted delivery of chemotherapeutic agents

2015 ◽  
Vol 6 (8) ◽  
pp. 1286-1299 ◽  
Author(s):  
D. D. Lane ◽  
D. Y. Chiu ◽  
F. Y. Su ◽  
S. Srinivasan ◽  
H. B. Kern ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Targeted Delivery ◽  
Raft Polymerization ◽  
Chemotherapeutic Agents ◽  
Polymer Nanoparticles ◽  
Drug Delivery Vehicles ◽  
Molecular Weights ◽  
Delivery Vehicles ◽  
Targeted Drug

Second generation polymeric brushes with molecular weights in excess of 106 Da were synthesize via RAFT polymerization for use as antibody targeted drug delivery vehicles.

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